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Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") users: relationship to cognitive performance.
Psychopharmacology (Berl). 2008 Oct; 200(3):439-50.P

Abstract

BACKGROUND

(+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance.

MATERIALS AND METHODS

Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing.

RESULTS

MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship.

CONCLUSIONS

Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.

Authors+Show Affiliations

Department of Psychiatry, The Johns Hopkins School of Medicine, Baltimore, MD 21224, USA. umccann@jhmi.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18661256

Citation

McCann, Una D., et al. "Positron Emission Tomographic Studies of Brain Dopamine and Serotonin Transporters in Abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") Users: Relationship to Cognitive Performance." Psychopharmacology, vol. 200, no. 3, 2008, pp. 439-50.
McCann UD, Szabo Z, Vranesic M, et al. Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") users: relationship to cognitive performance. Psychopharmacology (Berl). 2008;200(3):439-50.
McCann, U. D., Szabo, Z., Vranesic, M., Palermo, M., Mathews, W. B., Ravert, H. T., Dannals, R. F., & Ricaurte, G. A. (2008). Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") users: relationship to cognitive performance. Psychopharmacology, 200(3), 439-50. https://doi.org/10.1007/s00213-008-1218-4
McCann UD, et al. Positron Emission Tomographic Studies of Brain Dopamine and Serotonin Transporters in Abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") Users: Relationship to Cognitive Performance. Psychopharmacology (Berl). 2008;200(3):439-50. PubMed PMID: 18661256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") users: relationship to cognitive performance. AU - McCann,Una D, AU - Szabo,Zsolt, AU - Vranesic,Melin, AU - Palermo,Michael, AU - Mathews,William B, AU - Ravert,Hayden T, AU - Dannals,Robert F, AU - Ricaurte,George A, Y1 - 2008/07/27/ PY - 2007/12/21/received PY - 2008/05/28/accepted PY - 2008/7/29/pubmed PY - 2009/2/10/medline PY - 2008/7/29/entrez SP - 439 EP - 50 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 200 IS - 3 N2 - BACKGROUND: (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. MATERIALS AND METHODS: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [11C]WIN 35,428 and [11C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. RESULTS: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. CONCLUSIONS: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18661256/Positron_emission_tomographic_studies_of_brain_dopamine_and_serotonin_transporters_in_abstinent__+/__34_methylenedioxymethamphetamine__"ecstasy"__users:_relationship_to_cognitive_performance_ L2 - https://dx.doi.org/10.1007/s00213-008-1218-4 DB - PRIME DP - Unbound Medicine ER -